Solid Cancer, Urological Cancer
Conditions
Brief summary
This study is an open-label, multicenter, dose-escalation and dose-expansion, non-randomized phase I clinical study evaluating the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of SI-B036 bispecific antibody injection in patients with locally advanced or metastatic urological tumors and other solid tumors.
Detailed description
The study consists of two phases: a dose-escalation phase (Phase Ia) and a dose-expansion phase (Phase Ib).
Interventions
DRUGSI-B036
Administration by intravenous infusion for a cycle of 3 weeks.
Sponsors
Sichuan Baili Pharmaceutical Co., Ltd.
Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntarily sign the informed consent form and agree to comply with the protocol requirements; 2. No gender restriction; 3. Age: ≥ 18 years and ≤ 75 years; 4. Expected survival time ≥ 3 months; 5. Locally advanced or metastatic urological tumors and other solid tumors; 6. Agree to provide archived tumor tissue specimens collected within 2 years from the primary or metastatic lesion, or fresh tissue samples; 7. Must have at least one measurable lesion as defined by RECIST v1.1; 8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 9. Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0; 10. No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥ 50%; 11. Organ function levels must meet the specified requirements; 12. Coagulation function: International Normalized Ratio (INR) ≤ 1.5, and activated partial thromboplastin time (aPTT) ≤ 1.5 × upper limit of normal (ULN); 13. Urine protein ≤ 1+ or ≤ 1000 mg/24h; 14. For premenopausal women of childbearing potential, a serum pregnancy test must be performed within 7 days prior to the start of treatment, with a negative result, and they must not be breastfeeding; all enrolled patients (regardless of male or female) must use adequate barrier contraception throughout the entire treatment period and for 6 months after the completion of treatment; 15. The trial participant must be willing and able to comply with the visit schedule, treatment plan, laboratory tests, and other study-related procedures as specified in the protocol.
Exclusion criteria
1. Use of chemotherapy, biotherapy, immunotherapy, or similar treatments within 4 weeks or 5 half-lives prior to the first dose; 2. Receipt of immunosuppressive therapy within 2 weeks prior to the first dose; 3. History of severe cardiac or cerebrovascular disease; 4. Prolonged QTc interval, complete left bundle branch block, third-degree atrioventricular block, or frequent and uncontrolled arrhythmias; 5. Active autoimmune diseases and inflammatory diseases; 6. Prior history of ≥ Grade 3 toxicity related to anti-angiogenic therapy when receiving such treatment previously; 7. Diagnosis of another solid tumor within 5 years prior to the first dose; 8. Unstable thrombotic events requiring therapeutic intervention within 6 months prior to the first dose; 9. Uncontrolled hypertension; 10. Diabetes mellitus with poor glycemic control; 11. History of interstitial lung disease (ILD) requiring corticosteroid therapy, or current ILD, or ≥ Grade 2 radiation pneumonitis; 12. Concurrent pulmonary disease resulting in severe impairment of respiratory function; 13. Active central nervous system (CNS) metastases; 14. History of hypersensitivity to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient of SI-B036; 15. Prior history of organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT); 16. Positive for human immunodeficiency virus (HIV) antibodies, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection; 17. Active infection requiring systemic therapy within 4 weeks prior to the first dose of the study drug; 18. Presence of pleural, abdominal, or pelvic effusion, or pericardial effusion requiring drainage and/or associated with symptoms within 4 weeks prior to the first dose of the study drug; 19. Imaging findings indicating that the tumor has invaded or encased the great thoracic vessels, pericardium, or heart; 20. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks prior to screening; 21. History of fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to the first dose; 22. Use of another investigational drug within 4 weeks or 5 half-lives prior to the first dose; 23. Pregnant or lactating women; 24. Other conditions that, in the investigator's opinion, make the subject unsuitable for participation in this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ia: Maximum tolerated dose (MTD) | Up to 21 days after the first dose | MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle. |
| Phase Ib: Recommended Phase II Dose (RP2D) | Up to approximately 24 months | The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of SI-B036. |
| Phase Ia: Dose limiting toxicity (DLT) | Up to 21 days after the first dose | DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Emergent Adverse Event (TEAE) | Up to approximately 24 months | TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of SI-B036. The type, frequency and severity of TEAE will be evaluated during the treatment of SI-B036. |
| Cmax | Up to approximately 24 months | Cmax is defined as the maximum observed drug concentration in plasma after administration. |
| Tmax | Up to approximately 24 months | Tmax is defined as the time required to reach the maximum drug concentration in plasma following drug administration. |
| T1/2 | Up to approximately 24 months | T1/2 is defined as the time required for the plasma concentration of a drug to decrease by 50% during the elimination phase. |
| AUC0-t | Up to approximately 24 months | AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration. |
| CL (Clearance) | Up to approximately 24 months | Clearance (CL) is the volume of plasma from which a drug is completely removed per unit time. |
| Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration prior to the next dose will be administered. |
| Anti-drug Antibody (ADA) | Up to approximately 24 months | Frequency of anti-SI-B036 antibody (ADA) will be investigated. |
| Progression-free Survival (PFS) | Up to approximately 24 months | Progression-free survival (PFS) as assessed by BICR is defined as the time between the date subjects were randomized and the first observation of disease progression (based on BICR's image-based assessment) or death. |
| Objective Response Rate (ORR) | Up to approximately 24 months | Objective response rate (ORR) is defined as the number of CR and PR in the treatment and control groups divided by the number of that group in the full analysis set (FAS). |
| Disease Control Rate (DCR) | Up to approximately 24 months | Disease Control Rate (DCR) : Percentage of all randomized subjects who rated the best overall response (BOR) as complete response (CR), partial response (PR), and disease stabilization (SD) according to RECIST 1.1 criteria. |
| Duration of Response (DOR) | Up to approximately 24 months | Duration of Response (DOR) : defined as the period from the date when tumor response is first recorded to the date when objective tumor progression is first recorded or the date of death. |
Countries
China
Contacts
CONTACTSa Xiao
Outcome results
None listed